These findings suggest that allogeneic HSCT may overcome the unfavorable impact of t(6; 9)(p23; q34) as an independent prognostic factor. Leukemia (2012) 26, 461-464; doi:10.1038/leu.2011.229; published online 26 August 2011″
“Introduction: The sigma(1) ligands are considered to be a new class of potential therapeutic agents for several types of central nervous system check details disorder.
Carbon-11-labeled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([C-11]SA4503) was shown to be a promising PET ligand for mapping sigma(1) receptors, and was applied to measure receptor occupancy with several therapeutic drugs in the living human brain. In this study, we applied this technique for preclinical in vivo screening of novel sigma(1) selective agonists.
Methods: Six newly synthesized piperazine derivatives containing arylalkylamine groups and cyclohexylamine derivatives containing phenyl groups were selected and tested for their in vivo sigma(1) receptor binding with [C-11]SA4503.
The test compounds were administered by intravenous co-injection or oral administration. The in vivo receptor binding of [C-11]SA4503 was evaluated by a tissue dissection method at a single time point.
Results: Our in vivo screen identified the most promising candidate of novel sigma(1) agonist in the piperazine derivatives. Some correlations between in vitro affinity and in vivo receptor blocking rate were observed when considering see more oral bioavailability. In vivo receptor blocking of piperazine derivatives after oral administration may be predictable by simple co-injection study.
Conclusion: Ligand selection
with [C-11]SA4503 by the in vivo receptor binding assay was performed successfully. This technique is a practical and high-throughput method that can directly evaluate blood-brain barrier permeability, receptor binding, and bioavailability of drug candidates at the same time. (C) 2012 Elsevier Inc. All rights reserved.”
“The PcF protein from Phytophthora cactorum is the first member of the “”PcF toxin family”" from the plant PFKL pathogens Phytophthora spp. It is able to induce withering in tomato and strawberry leaves. The lack of sequence similarity with other proteins hampers the identification of the molecular mechanisms responsible for its toxicity. Here, we show that the six cysteines form a disulphide pattern that is exclusive for PcF and essential for the protein withering activity. The NMR solution structure identifies a novel fold among protein effectors: a helix-loop-helix motif. The presence of a negatively charged surface suggests that it might act as a site of electrostatic interaction. Interestingly, a good fold match with Ole e 6, a plant protein with allergenic activity, highlighted the spatial superimposition of a stretch of identical residues. This finding suggests a possible biological activity based on molecular mimicry.